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13 pages, 2825 KiB

Open AccessArticle

Outcome Disparities in Patients with Early-Stage Laryngeal Cancer Depending on Localization, Tobacco Consumption, and Treatment Modality

by Theresa Wald, Tim-Jonathan Koppe, Markus Pirlich, Veit Zebralla, Viktor Kunz, Andreas Dietz, Matthaeus Stoehr and Gunnar Wichmann

Biomedicines 2024, 12(9), 2136; https://doi.org/10.3390/biomedicines12092136 - 20 Sep 2024

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Abstract

Background/Objectives: Laryngeal squamous cell carcinoma (LSCC) is among most frequent malignancies of the head and neck. Recent oncologic research focusses on advanced rather than on early stages. Thus, we aimed to improve the knowledge concerning prognostic factors and survival in early glottic (GC) [...] Read more.

Background/Objectives: Laryngeal squamous cell carcinoma (LSCC) is among most frequent malignancies of the head and neck. Recent oncologic research focusses on advanced rather than on early stages. Thus, we aimed to improve the knowledge concerning prognostic factors and survival in early glottic (GC) and supraglottic cancer (SGC). Methods: We retrospectively investigated patients diagnosed in 2007 to 2020 with stage I or II GC (ICD-10-C32.0) or SGC (ICD-10-C32.1, C32.8 or C32.9). For precise discrimination of GC and SGC, pathology reports about biopsy and definitive excision were closely examined and information on clinical characteristics and risk factors were collected before analyzing patterns of risk factors for overall survival (OS) in multivariate Cox regression analyses (mvCox). Results: The cohort included 220 patients with early GC (n = 183) and SGC (n = 37). The GC patients showed significantly improved 5-year OS compared to SGC patients (83.6% vs. 64.9%; p = 0.004), whereas survival according to UICC stage (I vs. II) was not different (p = 0.177). Surgical resection was superior to definitive radiotherapy (RT) for 5-year OS (p < 0.001). Cumulative tobacco consumption of greater than 10 pack years drastically impaired OS (p = 0.024), especially in patients receiving RT (p < 0.001). Supraglottic localization, smoking, and re-resection after initial R1 status consistently were independent prognostic factors in mvCox. Conclusions: Our cohort of early LSCC patients demonstrates significant negative impact of supraglottic localization, older age, tobacco consumption, poor tumor differentiation, and re-resection on OS. Further research is required as there is still lack of evidence on optimal decision-making and therapeutic strategies. Full article

(This article belongs to the Special Issue Head and Neck Tumors, 3rd Edition)

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14 pages, 799 KiB

Open AccessArticle

Prognosis of Pneumonia in Head and Neck Squamous Cell Carcinoma Patients Who Received Concurrent Chemoradiotherapy

by Tzu-Hsun Kao, Tai-Jan Chiu, Ching-Nung Wu, Shao-Chun Wu, Wei-Chih Chen, Yao-Hsu Yang, Yu-Ming Wang and Sheng-Dean Luo

Biomedicines 2024, 12(7), 1480; https://doi.org/10.3390/biomedicines12071480 - 4 Jul 2024

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Abstract

Concurrent chemoradiotherapy (CCRT) is the standard treatment for patients with locally advanced squamous cell carcinoma of the head and neck (HNSCC). Pneumonia is a significant complication in these patients. This study aims to identify pneumonia risk factors and their impact on survival in [...] Read more.

Concurrent chemoradiotherapy (CCRT) is the standard treatment for patients with locally advanced squamous cell carcinoma of the head and neck (HNSCC). Pneumonia is a significant complication in these patients. This study aims to identify pneumonia risk factors and their impact on survival in HNSCC patients undergoing CCRT. Data from the Chang Gung Research Database (CGRD) were retrospectively reviewed for patients treated between January 2007 and December 2019. Of 6959 patients, 1601 (23.01%) developed pneumonia, resulting in a median overall survival (OS) of 1.2 years compared to 4.9 years in the non-pneumonia group (p < 0.001). The pneumonia group included older patients with advanced tumors, more patients with diabetes mellitus (DM), more patients with invasive procedures, longer chemotherapy and radiotherapy durations, and lower body weight. The 2-year, 5-year, and 10-year OS rates were significantly lower in the pneumonia group. Multivariate analysis identified alcohol consumption, DM, gastrostomy, nasogastric tube use, longer chemotherapy, and a 2-week radiotherapy delay as independent risk factors. Understanding these risks can lead to early interventions to prevent severe pneumonia-related complications. A better understanding of the risks of pneumonia enables early and aggressive interventions to prevent severe complications. Full article

(This article belongs to the Special Issue Head and Neck Tumors, 3rd Edition)

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11 pages, 842 KiB

Open AccessArticle

Efficacy of Office-Based Salivary Ductal Steroid Irrigation for Managing Post-Irradiation Xerostomia in Head and Neck Cancer Patients: A Retrospective Study

by Yen-Chun Chen, Nguyen-Kieu Viet-Nhi, Luong Huu Dang, Chin-Hui Su and Shih-Han Hung

Biomedicines 2024, 12(5), 1033; https://doi.org/10.3390/biomedicines12051033 - 8 May 2024

Cited by 1 | Viewed by 994

Abstract

Post-irradiation xerostomia remains a significant quality of life concern for patients with head and neck cancers. Conventional therapies offer limited effectiveness. This study aims to investigate the therapeutic potential of office-based salivary ductal steroid irrigation in patients with post-irradiation xerostomia. This single-center observational [...] Read more.

Post-irradiation xerostomia remains a significant quality of life concern for patients with head and neck cancers. Conventional therapies offer limited effectiveness. This study aims to investigate the therapeutic potential of office-based salivary ductal steroid irrigation in patients with post-irradiation xerostomia. This single-center observational study recruited 147 head and neck cancer patients suffering from post-irradiation xerostomia between November 2020 and October 2022. All included subjects received at least one round of successful salivary ductal cannulation and irrigation. The primary measure of efficacy was improvement in subjective xerostomia and objective salivary amylase levels. A logistic regression was employed to evaluate factors affecting treatment responsiveness. The response rate among nasopharyngeal cancer (NPC) patients was 74.8%, and that among non-NPC cancer was 65.6%, without significant intergroup differences. The statistical analysis revealed no significant influence of age, gender, or disease stage on treatment responsiveness. Post-treatment salivary amylase levels were significantly higher in responsive non-NPC patients. In conclusion, salivary ductal steroid irrigation emerged as a promising therapeutic modality for the management of post-irradiation xerostomia in head and neck cancer patients. While no explicit factors were predictive of responsiveness, the high rate of symptom improvement suggests that this therapy may be a viable alternative for patients that are refractory to standard treatments. Full article

(This article belongs to the Special Issue Head and Neck Tumors, 3rd Edition)

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11 pages, 258 KiB

Open AccessArticle

Global DNA Methylation Level in Tumour and Margin Samples in Relation to Human Papilloma Virus and Epstein–Barr Virus in Patients with Oropharyngeal and Oral Squamous Cell Carcinomas

by Jadwiga Gaździcka, Krzysztof Biernacki, Karolina Gołąbek, Katarzyna Miśkiewicz-Orczyk, Natalia Zięba, Maciej Misiołek and Joanna Katarzyna Strzelczyk

Biomedicines 2024, 12(4), 914; https://doi.org/10.3390/biomedicines12040914 - 20 Apr 2024

Viewed by 1093

Abstract

Background: Aberrant DNA methylation is a common epigenetic modification in cancers, including oropharyngeal squamous cell carcinoma (OPSCC) and oral squamous cell carcinoma (OSCC). Therefore, the analysis of methylation levels appears necessary to improve cancer therapy and prognosis. Methods: The enzyme-linked immunosorbent assay (ELISA) [...] Read more.

Background: Aberrant DNA methylation is a common epigenetic modification in cancers, including oropharyngeal squamous cell carcinoma (OPSCC) and oral squamous cell carcinoma (OSCC). Therefore, the analysis of methylation levels appears necessary to improve cancer therapy and prognosis. Methods: The enzyme-linked immunosorbent assay (ELISA) was used to analyse global DNA methylation levels in OPSCC and OSCC tumours and the margin samples after DNA isolation. HPV detection was conducted by hybridisation using GenoFlow HPV Array Test Kits (DiagCor Bioscience Inc., Hong Kong, China). EBV detection was performed using real-time PCR with an EBV PCR Kit (EBV/ISEX/100, GeneProof, Brno, Czech Republic). Results: OPSCC tumour samples obtained from women showed lower global DNA methylation levels than those from men (1.3% vs. 3.5%, p = 0.049). The margin samples from OPSCC patients with HPV and EBV coinfection showed global DNA methylation lower than those without coinfection (p = 0.042). G3 tumours from OSCC patients had significantly lower levels of global DNA methylation than G2 tumours (0.98% ± 0.74% vs. 3.77% ± 4.97%, p = 0.010). Additionally, tumours from HPV-positive OSCC patients had significantly lower global DNA methylation levels than those from HPV-negative patients (p = 0.013). In the margin samples, we observed a significant negative correlation between global DNA methylation and the N stage of OSCC patients (rS = −0.33, p = 0.039). HPV-positive OPSCC patients had higher global DNA methylation levels than HPV-positive OSCC patients (p = 0.015). Conclusion: We confirmed that methylation could be changed in relation to viral factors, such as HPV and EBV, as well as clinical and demographical parameters. Full article

(This article belongs to the Special Issue Head and Neck Tumors, 3rd Edition)

14 pages, 1252 KiB

Open AccessArticle

Friend or Foe? Exploring the Role of Cytomegalovirus (HCMV) Infection in Head and Neck Tumors

by Aleksandar Trivic, Jovica Milovanovic, Djurdjina Kablar, Ana Tomic, Miljan Folic, Ana Jotic, Nada Tomanovic, Ana Marija Tomic, Igor Djoric and Marko Jankovic

Biomedicines 2024, 12(4), 872; https://doi.org/10.3390/biomedicines12040872 - 15 Apr 2024

Cited by 1 | Viewed by 1483

Abstract

Although not regarded as an oncogenic pathogen, the human cytomegalovirus (HCMV) has been associated with a wide array of malignancies. Conversely, a number of studies report on possible anti-tumor properties of the virus, apparently mediated via HCMV-galvanized T-cell tumor killing; these were recently [...] Read more.

Although not regarded as an oncogenic pathogen, the human cytomegalovirus (HCMV) has been associated with a wide array of malignancies. Conversely, a number of studies report on possible anti-tumor properties of the virus, apparently mediated via HCMV-galvanized T-cell tumor killing; these were recently being investigated in clinical trials for the purposes of anti-cancer treatment by means of dendritic cell vaccines and HCMV-specific cytotoxic T cells. In the present study, we have analyzed the relation between a complement of head-and-neck tumors and HCMV infection across 73 countries worldwide using Spearman correlation, univariate and multivariate regression analysis. Intriguingly, HCMV was found to be pro-oncogenic in patients with nasopharyngeal carcinoma; contrarywise, the virus manifested an inverse (i.e., anti-tumor) association with the tumors of the lip/oral region and the salivary glands. Although this putative protective effect was noted initially for thyroid neoplasia and hypopharyngeal tumors as well, after multivariate regression analysis the connection did not hold. There was no association between laryngeal cancer and HCMV infection. It would appear that, depending on the tissue, HCMV may exert both protective and oncogenic effects. The globally observed protective feature of the virus could potentially be utilized in future therapeutic approaches for salivary tumors and neoplasia in the lip/oral region. As correlation does not necessarily imply causation, more in-depth molecular analyses from comprehensive clinical studies are warranted to substantiate our findings. Full article

(This article belongs to the Special Issue Head and Neck Tumors, 3rd Edition)

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21 pages, 1539 KiB

Open AccessArticle

Exploring the Link between Inflammatory Biomarkers and Head and Neck Cancer: Understanding the Impact of Smoking as a Cancer-Predisposing Factor

by Jarosław Nuszkiewicz, Joanna Wróblewska, Marlena Budek, Jolanta Czuczejko, Alina Woźniak, Marta Maruszak-Parda and Karolina Szewczyk-Golec

Biomedicines 2024, 12(4), 748; https://doi.org/10.3390/biomedicines12040748 - 27 Mar 2024

Cited by 1 | Viewed by 1254

Abstract

Head and neck cancer (HNC) is associated with significant morbidity globally, with smoking recognized as a key risk factor. This study investigates the interplay between smoking and inflammatory biomarkers in HNC development. The study involved 50 HNC patients, divided into smoking and non-smoking [...] Read more.

Head and neck cancer (HNC) is associated with significant morbidity globally, with smoking recognized as a key risk factor. This study investigates the interplay between smoking and inflammatory biomarkers in HNC development. The study involved 50 HNC patients, divided into smoking and non-smoking groups, and a control group of 30 healthy individuals. Serum levels of 48 cytokines, chemokines, growth factors, and other inflammatory markers were meticulously assessed. Significant differences in the levels of an extensive panel of inflammatory markers were observed between the patient groups and healthy controls. Elevated macrophage colony-stimulating factor (M-CSF) in both HNC groups implicated increased activity in pathways known for immunomodulation, proliferation, and angiogenesis during HNC cancerogenesis. In contrast, non-smokers with HNC demonstrated higher levels of interleukin 10 (IL-10) and interleukin 15 (IL-15), suggesting a more robust immune response. Platelet-derived growth factor BB (PDGF-BB) levels were particularly high in smokers with HNC. Smoking seems to alter the levels of crucial biomarkers in HNC, potentially affecting disease progression and responses to treatment. The data indicate that smokers may experience a more aggressive cancer phenotype, while non-smokers maintain a profile suggestive of a more active and effective immune response against HNC. Full article

(This article belongs to the Special Issue Head and Neck Tumors, 3rd Edition)

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17 pages, 5258 KiB

Open AccessArticle

Gene-Expression Patterns of Tumor and Peritumor Tissues of Smoking and Non-Smoking HPV-Negative Patients with Head and Neck Squamous Cell Carcinoma

by Anna Soboleva, Irina Arutyunyan, Enar Jumaniyazova, Polina Vishnyakova, Daria Zarubina, Eldar Nimatov, Andrey Elchaninov and Timur Fatkhudinov

Biomedicines 2024, 12(3), 696; https://doi.org/10.3390/biomedicines12030696 - 21 Mar 2024

Cited by 2 | Viewed by 2190

Abstract

We studied the gene-expression patterns in specimens of tumor and peritumor tissue biopsies of 26 patients with head and neck carcinomas depending on smoking status. Histological and immunohistochemical examinations verified that all tumors belonged to the “classical” subgroup of head and neck carcinomas, [...] Read more.

We studied the gene-expression patterns in specimens of tumor and peritumor tissue biopsies of 26 patients with head and neck carcinomas depending on smoking status. Histological and immunohistochemical examinations verified that all tumors belonged to the “classical” subgroup of head and neck carcinomas, and the HPV-negative tumor status was confirmed. The expression of 28 tumor-associated genes determined by RT-PCR was independent of patients’ sex or age, TNM status, degree of differentiation, or tissue localization. Moreover, in peritumor tissue, none of the 28 genes were differentially expressed between the groups of smoking and nonsmoking patients. During oncotransformation in both studied groups, there were similar processes typical for HNSCC progression: the expression levels of paired keratins 4 and 13 were reduced, while the expression levels of keratin 17 and CD44 were significantly increased. However, further investigation revealed some distinctive features: the expression of the genes EGFR and TP63 increased significantly only in the nonsmoking group, and the expression of IL6, CDKN2A, EGF, and PITX1 genes changed only in the smoking group. In addition, correlation analysis identified several clusters within which genes displayed correlations in their expression levels. The largest group included 10 genes: TIMP1, TIMP2, WEE1, YAP, HIF1A, PI3KCA, UTP14A, APIP, PTEN, and SLC26A6. The genetic signatures associated with smoking habits that we have found may serve as a prerequisite for the development of diagnostic panels/tests predicting responses to different therapeutic strategies for HNSCC. Full article

(This article belongs to the Special Issue Head and Neck Tumors, 3rd Edition)

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17 pages, 3963 KiB

Open AccessArticle

Genetic Mutations Associated with Inflammatory Response Caused by HPV Integration in Oropharyngeal Squamous Cell Carcinoma

by Mai Atique, Isis Muniz, Fatemeh Farshadi, Michael Hier, Alex Mlynarek, Marco Macarella, Mariana Maschietto, Belinda Nicolau, Moulay A. Alaoui-Jamali and Sabrina Daniela da Silva

Biomedicines 2024, 12(1), 24; https://doi.org/10.3390/biomedicines12010024 - 21 Dec 2023

Cited by 1 | Viewed by 2134

Abstract

(1) Background: Head and neck cancer (HNC) ranks as the sixth most prevalent cancer in the world. In addition to the traditional risk factors such as alcohol and tobacco consumption, the implication of the human papillomavirus (HPV) is becoming increasingly significant, particularly in [...] Read more.

(1) Background: Head and neck cancer (HNC) ranks as the sixth most prevalent cancer in the world. In addition to the traditional risk factors such as alcohol and tobacco consumption, the implication of the human papillomavirus (HPV) is becoming increasingly significant, particularly in oropharyngeal cancer (OPC). (2) Methods: This study is based on a review analysis of different articles and repositories investigating the mutation profile of HPV-related OPC and its impact on patient outcomes. (3) Results: By compiling data from 38 datasets involving 8311 patients from 12 countries, we identified 330 genes that were further analyzed. These genes were enriched for regulation of the inflammatory response (RB1, JAK2, FANCA, CYLD, SYK, ABCC1, SYK, BCL6, CEBPA, SRC, BAP1, FOXP1, FGR, BCR, LRRK2, RICTOR, IGF1, and ATM), among other biological processes. Hierarchical cluster analysis showed the most relevant biological processes were linked with the regulation of mast cell cytokine production, neutrophil activation and degranulation, and leukocyte activation (FDR < 0.001; p-value < 0.05), suggesting that neutrophils may be involved in the development and progression of HPV-related OPC. (4) Conclusions: The neutrophil infiltration and HPV status emerge as a potential prognostic factor for OPC. HPV-infected HNC cells could potentially lead to a decrease in neutrophil infiltration. By gaining a better molecular understanding of HPV-mediated neutrophil immunosuppression activity, it is possible to identify a meaningful target to boost antitumor immune response in HNC and hence to improve the survival of patients with HNC. Full article

(This article belongs to the Special Issue Head and Neck Tumors, 3rd Edition)

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11 pages, 995 KiB

Open AccessArticle

Immunohistochemical Assessment of Microvessel Density in OSCC: Spatial Heterogeneity of Angiogenesis and Its Impact on Survival

by Andreas Mamilos, Alexander Lein, Lina Winter, Markus Haas, Torsten E. Reichert, Tobias Ettl, Julian Künzel, Gerrit Spanier and Christoph Brochhausen

Biomedicines 2023, 11(10), 2724; https://doi.org/10.3390/biomedicines11102724 - 8 Oct 2023

Cited by 3 | Viewed by 1388

Abstract

(1) Background Oral squamous cell carcinomas (OSCC) are a common malignancy of the oral cavity and are often diagnosed when they have already spread to the regional lymph nodes. Advanced stages of cancer are characterized by the development of distant metastases. Angiogenesis, a [...] Read more.

(1) Background Oral squamous cell carcinomas (OSCC) are a common malignancy of the oral cavity and are often diagnosed when they have already spread to the regional lymph nodes. Advanced stages of cancer are characterized by the development of distant metastases. Angiogenesis, a hallmark of cancer, is known to contribute to cancer progression and metastasis. High microvessel density (MVD) has been linked to poor clinical outcomes in various types of cancer. (2) Methods: In this study, we aimed to investigate the spatial heterogeneity of blood vessels by comparing the tumor center and invasion front and to evaluate its prognostic value in OSCC. A total of 71 OSCC patient specimens were collected. The tissue was immunohistochemically stained using CD31 antibody to assess the MVD in the tumor center and the invasion front. Furthermore, the associations between the histopathological parameters, including MVD, disease-free survival (DFS), and overall survival (OS) were computed. (3) Results: In our study, we found a significantly higher presence of blood vessels at the invasion front of OSCCs compared to the tumor center. However, we did not observe any significant differences in MVD between different tumor stages. High intratumoral MVD was shown to be a positive prognostic factor for DFS (p = 0.047). (4) Conclusions: To the best of our knowledge, we were the first to analyze MVD as a prognostic factor by considering its spatial heterogeneity in OSCC. However, further studies are warranted to further elucidate the complexity of microvascular spatial heterogeneity and its influence on prognosis. Full article

(This article belongs to the Special Issue Head and Neck Tumors, 3rd Edition)

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Review

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11 pages, 238 KiB

Open AccessReview

Neoadjuvant Immunotherapy in Head and Neck Cancers: A Paradigm Shift in Treatment Approach

by Alessia Zotta, Maria Luisa Marciano, Francesco Sabbatino, Alessandro Ottaiano, Marco Cascella, Monica Pontone, Massimo Montano, Ester Calogero, Francesco Longo, Morena Fasano, Teresa Troiani, Fortunato Ciardiello, Fabiana Raffaella Rampetta, Giovanni Salzano, Giovanni Dell’Aversana Orabona, Luigi Califano, Franco Ionna and Francesco Perri

Biomedicines 2024, 12(10), 2337; https://doi.org/10.3390/biomedicines12102337 - 14 Oct 2024

Viewed by 568

Abstract

Checkpoint inhibitors (ICIs) have demonstrated substantial efficacy in the treatment of numerous solid tumors, including head and neck cancer. Their inclusion in the therapeutic paradigm in metastatic lines of treatment has certainly improved the outcomes of these patients. Starting from this assumption, numerous [...] Read more.

Checkpoint inhibitors (ICIs) have demonstrated substantial efficacy in the treatment of numerous solid tumors, including head and neck cancer. Their inclusion in the therapeutic paradigm in metastatic lines of treatment has certainly improved the outcomes of these patients. Starting from this assumption, numerous studies have been conducted on ICIs in other earlier disease settings, including studies conducted in patients in neoadjuvant settings. However, how many and which studies are truly significant? Can they lay concrete foundations for further future studies and therefore allow us to continue to have this interesting future perspective? Through a review of the existing literature, coupled with insights gleaned from clinical practice and from the main recently published studies, we aim to examine the therapeutic potential of ICIs in patients affected by head and neck cancer in a neoadjuvant treatment setting and encourage researchers to set up successful future clinical trials. Full article

(This article belongs to the Special Issue Head and Neck Tumors, 3rd Edition)

18 pages, 744 KiB

Open AccessReview

Potential Immunohistochemical Biomarkers for Grading Oral Dysplasia: A Literature Review

by Jakub Zdrojewski, Monika Nowak, Kacper Nijakowski, Jakub Jankowski, Andrea Scribante, Simone Gallo, Maurizio Pascadopoli and Anna Surdacka

Biomedicines 2024, 12(3), 577; https://doi.org/10.3390/biomedicines12030577 - 5 Mar 2024

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Abstract

Oral cancer is a prevalent global health issue, with significant morbidity and mortality rates. Despite available preventive measures, it remains one of the most common cancers, emphasising the need for improved diagnostic and prognostic tools. This review focuses on oral potentially malignant disorders [...] Read more.

Oral cancer is a prevalent global health issue, with significant morbidity and mortality rates. Despite available preventive measures, it remains one of the most common cancers, emphasising the need for improved diagnostic and prognostic tools. This review focuses on oral potentially malignant disorders (OPMDs), precursors to oral cancer, specifically emphasising oral epithelial dysplasia (OED). The World Health Organisation (WHO) provides a three-tier grading system for OED, and recent updates have expanded the criteria to enhance diagnostic precision. In the prognostic evaluation of OED, histological grading is presently regarded as the gold standard; however, its subjectivity and unreliability in anticipating malignant transformation or recurrence pose notable limitations. The primary objective is to investigate whether specific immunohistochemical biomarkers can enhance OED grading assessment according to the WHO classification. Biomarkers exhibit significant potential for comprehensive cancer risk evaluation, early detection, diagnosis, prognosis, and treatment optimisation. Technological advancements, including sequencing and nanotechnology, have expanded detection capabilities. Some analysed biomarkers are most frequently chosen, such as p53, Ki-67, cadherins/catenins, and other proteins used to differentiate OED grades. However, further research is needed to confirm these findings and discover new potential biomarkers for precise dysplasia grading and minimally invasive assessment of the risk of malignant transformation. Full article

(This article belongs to the Special Issue Head and Neck Tumors, 3rd Edition)

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22 pages, 2599 KiB

Open AccessReview

Role of Akt/Protein Kinase B in Cancer Metastasis

by Mohammad Islam, Sarah Jones and Ian Ellis

Biomedicines 2023, 11(11), 3001; https://doi.org/10.3390/biomedicines11113001 - 8 Nov 2023

Cited by 2 | Viewed by 1867

Abstract

Metastasis is a critical step in the process of carcinogenesis and a vast majority of cancer-related mortalities result from metastatic disease that is resistant to current therapies. Cell migration and invasion are the first steps of the metastasis process, which mainly occurs by [...] Read more.

Metastasis is a critical step in the process of carcinogenesis and a vast majority of cancer-related mortalities result from metastatic disease that is resistant to current therapies. Cell migration and invasion are the first steps of the metastasis process, which mainly occurs by two important biological mechanisms, i.e., cytoskeletal remodelling and epithelial to mesenchymal transition (EMT). Akt (also known as protein kinase B) is a central signalling molecule of the PI3K-Akt signalling pathway. Aberrant activation of this pathway has been identified in a wide range of cancers. Several studies have revealed that Akt actively engages with the migratory process in motile cells, including metastatic cancer cells. The downstream signalling mechanism of Akt in cell migration depends upon the tumour type, sites, and intracellular localisation of activated Akt. In this review, we focus on the role of Akt in the regulation of two events that control cell migration and invasion in various cancers including head and neck squamous cell carcinoma (HNSCC) and the status of PI3K-Akt pathway inhibitors in clinical trials in metastatic cancers. Full article

(This article belongs to the Special Issue Head and Neck Tumors, 3rd Edition)

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